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The characterization of synthetic and natural product pharmaceuticals by electrospray ionization-mass spectroscopy (ESI-MS) and liquid chromatography (LC)-ESI-MS
http://dx.doi.org/10.1016/j.trac.2006.04.003

Summary:
1) Introduction
  1. a. Discovery of ESI by Yamashita and Fenn; in 2002, the ESI discovery was awarded the Nobel Prize in Chemistry.
  2. b. Structural identification of molecules are obtained by MS and CID with triple-quadruple MS using ion-trap instrument.
  3. c. ESI is now considered an important ionization technique in drug molecules in matrix such as food, pharmaceutical formulation and body fluids.
  4. d. ESI-MS applications on small molecular masses as well as bioactive peptides.
  5. e. Drugs used to analyze include amine-containing side chains and N-containing saturated ring structures. Additional structures are quinolones and nicotines.
  6. f. Unknown structures analyzed are found in plants with antibacterial activity, and in frogs.

2) Drugs with amine-containing side chains
  1. a. Synthetic opiate agonist methadone’s spectrum was taken using ESI-MS and data retrieved correspond to known results presented by Joyce (author of another paper which this author is using as a source). Yet, the spectra results from ESI-MS contain valuable peaks which do not appear in the electron impact-mass spectrometry spectra.
  2. b. ESI-QToF-MS shows characteristics fragmentations of amine-containing side chains. Spectras of ESI-MS can be later of use as in cross referencing with data of unknown compounds.
  3. c. Samples of anti-depressant drugs were used in mixtures of low –ng/ml concentrations and they were identified using LC-ESI-MS.
  4. d. Saliva, similar to blood can be used to test drug use; four amino-containing side chains drugs were identified in the saliva using low-ng/ml concentration via LC-ESI-MS.
  5. e. Hair sample are also used to test for drug use; analysis using (GC)-MS and LC-MS are presented in court as vital evidence.
  6. f. Characterization of anti-psychotic drugs amine-containing side chains were done in lab using LC-ESI-MS. Results using LC-ESI-MS were found to have a higher concentration compared to GC-MS.
  7. g. Table 1: Range m/z 17-42 taken from sample molecules discussed. Used for cross-reference.
3) Drugs with nitrogen-containing saturated ring structures
  1. a. Structure prediction and fragmentation pathways of piperidines and piperazines were proposed by ESI-MS and supported by ESI-QToF-MS.
  2. b. Figure 1: LC-ESI-MS of 6 anti-depressant drugs; morphine is used as the standard
  3. c. Fig.2: Pethidine fragmentation using ESI-MS
  4. d. Table 2: Heat of formation of neutral molecules.
4) Flunitrazepam (Rohypnol) and other heterocyclic hypnotics
  1. a. Identification and quantitation of different concentrations of flunitrapezam using LC-ESI-MS.
  2. b. Molecules can become protonated by ES capillary or by protons present in impurities.
  3. c. In selected hypnotic drugs studies by ESI-MS, functional groups are cleaved as neutral molecules. Aromatic rings are also cleaved off.
  4. d. Figure 3: Molecular structures of selected hypnotic drugs.
5) Quinolines
  1. a. Unknown structures of quinolines alkaloids found in plants were studies using ESI-MS. Quinoline alkaloids data from ESI-MS, GC and LC were used to create databases.
  2. b. Acid extraction from leaves of Choisya ternate was analyzed by LC-ESI-MS and the peaks generated are studies.
  3. c. Table 3: Peaks recorded with retention time and m/z values.
  4. d. Figure 4: Structures of Quinoline derivatives.
  5. e. Retention time, m/z values are used in databases for reference.
6) Nicotines
  1. a. Studies of the fragmentation of alkaloid nicotine using ESI-MS and Q-ToF-MS2 are important for anti-smoking therapy products.
  2. b. Identification of peaks seen in the ESI-MS spectra of nicotine.
  3. c. Figure 5: Fragmentation pathway of nicotine
  4. d. Identification of peaks seen in the spectra of cotinine, which is the oxidized nicotine
  5. e. LC-ESI-MS is a new analytical method used for the identification of nicotine.
  6. f. Figure 6: Nicotine spectra of HPLC-ESI-MS and HPLC-UV.
7) ESI-MSn characterization of biologically active extracts of Australian bush medicines
  1. a. Using ESI-MS and HPLC-ESI-MS to study unknown molecular structures in extract from Australian plants.
  2. b. Characterization of a methanolic extract from Australian plant using TLC.
  3. c. Further characterization of methanolic extract
8) ESI-MS characterization of biologically-active peptides from frog venoms
  1. a. Isolating bioactive peptides from Australian Golden Bell Frog, Litoria aurea
  2. b. Peptides from frogs have shown to be very significant for human health conditions.
  3. c. Procedure for preparing the frog sample.
  4. d. Characterization of the bradykinin peptides.
  5. e. Figure 7: MS2 of the bradykinin and the threonine-6 variant.
  6. f. MS methods provide a short way to screen a peptide
  7. g. Experiments with bradykinin and threonine-6 bradykinin show muscle relaxation in rats.
  8. h. Peptide prospecting is shown to be work in isolating other peptides.